We propose to examine the hypothesis that a majority of aqueous outflow resistance is due to an accumulation of macromolecules in the extracellular spaces of the juxtacanalicular meshwork and further, that certain components of this resistance-causing material are contained in aqueous humor. We anticipate that confirmation of these hypotheses will identify factors which lead to elevated intraocular pressure and glaucoma. Our group has recently found that macromolecules present in aqueous humor dramatically affect the resistance to flow through microporous filters with pore dimensions similar to those of the juxtacanalicular meshwork. We propose to identify the important macromolecules in this process, study the physical mechanisms responsible for the entrapment of these substances, and develop a theoretical framework to model and predict the behavior of this immobilized matrix of macromolecules in the aqueous outflow passages.